Atopic dermatitis role

In the pathogenesis of many chronic inflammatory diseases (e.g., rheumatoid arthritis, glomerulonephritis, colitis ulcerosa, Morbus Crohn, atopic dermatitis, psoriasis) autoimmune processes play an important role, too. Although first of all nonsteroidal antiinflammatory agents or glucocorticoids should be applied, immunosuppressive agents may also be indicated. 

Novak N, Bieber T The role of dendritic cell sub-types in the pathophysiology of atopic dermatitis. J Am Acad Dermatol 2005 53 S171-S176. 

Beside the well-established role of Th2 cells in allergy, it also became clear that not only Th2, but also Thl cells can contribute to allergic pathology, specifically in atopic dermatitis such as in acute lesional skin [10], where IFN-y is known to induce cell death in keratinocytes causing the spongiform pathology observed in atopic dermatitis [11]. 

Takaoka A, Aral I, Sugimoto M, Yamaguchi A, Tanaka M, Nakaike S Expression of lL-31 gene transcripts in NC/Nga mice with atopic dermatitis. Eur J Pharmacol 2005 516 180-181. Grewe M, Bruijnzeel-Koomen CA, Schopf E, Thepen T, Langeveld-Wildschut AG, Ruzicka T, Krutmann J A role for Thl and Th2 ceUs in the immunopathogenesis of atopic dermatitis. Immunol Today 1998 19 359-361. 

Eczema does not occur in the absence ofT cells. Here we provide an overview on the regulatory impact which T cells have on the establishment and maintenance of atopic dermatitis. Particularly, we outline the role of different T-helper cell subsets (i.e.Th-l,Th-2,T-regulatory andTh-17 cells) and their distinct influence on the cutaneous inflammatory reaction at different stages of the disease. Eczema is characterized by epidermal inflammation and thus T-cell/ker-atinocyte interactions are of particular relevance in this condition. Alterations in innate and adaptive immunity involving cells result in susceptibility to skin infections and in hyperreactivity reactions to environmental stimuli which in turn determine the course and severity of atopic dermatitis. Copyright 2008 S. Karger AG, Basel... 

Role of Adaptive Immune Responses in Atopic Dermatitis Involving IgE Responses In about 80% of adult patients with atopic dermatitis, the disease is associated with increased serum IgE levels, sensitization against aeroallergens... 

A murine model of food-induced atopic dermatitis confirmed the important role of specific T cells in eczema here, C3H/HeJ mice were orally sensitized to cow s milk or peanut and thereafter exposed to the allergen. An eczematous eruption developed in approximately one third of mice after low-grade exposure to milk or peanut proteins. Histological examination of lesional skin revealed spongiosis and a cellular infiltrate mainly consisting of CD4-I- lymphocytes. 

The role of CD8-I- T cells in atopic skin inflammation is still not well defined. It has been shown that CLA-I-CD8-I- T cells isolated from the circulation are as potent as CLA+CD4-I- T cells in the induction of IgE and enhancement of eosinophil survival. This suggests that these cells have more than bystander functions in atopic dermatitis. Recent data from a mouse model indicate that allergen-primed CD8+ T cells are required for the development of atopic dermati-tis-like lesions in vivo [19]. 

IL-23 has recently been shown to be produced by dendritic cells and by human cultured keratinocytes in healthy skin and in psoriasis - its role in atopic dermatitis has to be defined [22]. Interaction of keratinocytes with activated T cells via CD40-CD40L may enhance IL-23 production and subsequently the IFN-y production by memory T cells [23]. 

In chronic lichenified atopic dermatitis skin lesions, fewer IL-4 and IL-13 mRNA-expressing cells are present, but greater numbers of IL-5, GM-CSF, IL-12, and IFN-y mRNA-expressing cells are detected. The rise in IL-5 expression during the transition from acute to chronic atopic dermatitis likely plays a role in the prolongation of eosinophil survival and function. Some of the other cytokines mentioned above support the function of macrophages and promote the Th-1-type... 

Th-17 cells appear to be involved in protection against bacterial pathogens. In addition, Th-17 cells may also be crucial in the pathogenesis of various chronic inflammatory diseases that were formerly categorized as Th-1-mediated disorders. Whereas IL-17 may play an important role in the pathogenesis of psoriasis and contact hypersensitivity, its role in atopic dermatitis is still unclear [36]. In skin biopsy specimens recovered from acute and chronic skin lesions from patients with atopic dermatitis, IL-17 was preferentially associated with acute lesions [37]. 

Werfel T, Breuer K Role of food allergy in atopic dermatitis. Curr Opin Allergy Clin Immunol 2004 4 379-385. 

Purwar R, Werfel T, Wittmann M IL-13-stimulated human keratinocytes preferentially attract CD4+CCR4+ T cells possible role in atopic dermatitis. J Invest Dermatol 2006 126 1043-1051. 

Baker BS The role of microorganisms in atopic dermatitis. Clin Exp Immunol 2006 144 1-9. 

Trautmann A, Akdis M, Brocket EB, Blaser K, Akdis CA New insights into the role of T cells in atopic dermatitis and allergic contact dermatitis. Trends Immunol 2001 22 530-532. 

Not surprisingly, the cutaneous microbiome has been studied for its potential role in dermatologic conditions such as psoriasis, atopic dermatitis, and acne. Psoriasis, a chronic idiopathic inflammatory disease of the skin (170), has been associated with an overrepresentation of Firmicutes and underrepresentation of Actinobacteria when compared to both the unaffected skin of psoriatic patients and the skin of normal controls (171). Additionally, Pro-teobacteria were detected less frequently in psoriatic lesions compared to skin of healthy controls (171). Subsequent studies using pyrosequencing techniques confirmed that Actinobacteria were more abundant in controls compared to patients with psoriasis however, Proteobacteria were significantly higher in trunk skin samples from psoriatic patients compared to controls (172). 

Miyamoto et al. have also demonstrated in the dry skin and itch mouse model (water + acetone ether treated) that the scratching response can be inhibited by the use of atropine, a nonspecific muscarinic acetylcholine receptor (mAChR) antagonist, and 4-diphenyl-acetoxy-N-methyl-piperidine (4-DAMP), an M3 mAChR antagonist.32 They further showed that Mi and M2 mAChR antagonist were not able to inhibit the scratch response. This report suggests the role of acetylcholine, and the M3 specific receptor as a potential player in dry-skin-associated pruritus. In addition, skin biopsies in human subjects with atopic dermatitis were found to have increased levels of acetylcholine compared with normal controls, which suggests that abnormal concentrations of neurotransmitters may also be involved in itch secondary to xeroderma.33... 

Importantly, not all moisturizers provide the same effect in restoration of the barrier function. Certain lipid mixtures or an inadequate concentration of physiologic lipids actually have been demonstrated to inhibit barrier restoration.42,43 Newer ceramide-dominant emollients have been developed in efforts to restore the intrinsic physiologic lipid concentration of the skin. One type of ceramide-dominant emollient was shown to significantly improve the overall severity of atopic dermatitis and demonstrated correction of transepidermal water losses in these patients.44 Unfortunately, studies using ceramide-dominant emollients for patients with atopic dermatitis did not use itch improvement as an endpoint. However, these types of moisturizers likely have a role in the improvement of itch associated with dry skin. 

---